A recent outbreak of human H1N2 infection: correspondence
Authors: Ranjit Sah, Aroop Mohanty, Ranjana Rohilla, Bijay K. Padhi
Journal: International Journal of Surgery (2023)

Highlights The swine host provides a 'mixing vessel' for the origin of pandemic viruses because they can be infected by both avian and human influenza A viruses. The Taiwan Centre for Disease Control and Prevention reported a type A influenza virus in October 2022 in a 7-year-old girl in central Taiwan. The pathogen was sequenced as the H1N2v influenza virus. Influenza A virus, a continuously evolving pathogen with an enveloped negative-sense RNA and segmented genome, infect a variety of hosts, including humans, birds, and swine. Generally, swine provides a 'mixing vessel' for the origin of pandemic viruses because they can be infected by both avian and human influenza A viruses. H1N1, H1N2, and H3N2 are major subtypes of influenza A viruses in pigs, and these occasionally cross the species barrier to infect humans sporadically. Recently, many such reports have been documented; these viruses are called 'variant viruses' and are denoted by adding a 'v' to the virus nomenclature. Variant swine viruses exhibit remarkable genetic and antigenic assortment and can prove a threat to human health, therefore, close monitoring for any abrupt genetic change is the need of the hour. Although not ordinarily transmitting to humans, these variant viruses have been proven to have vigorous replication and efficient droplet transmission in animal models like ferrets. As per available evidence, recent variant H1 viruses possess some genetic markers of concern, yet they can further adapt at any point in time to present a pandemic threat to humans. Moreover, zoonotic influenza viruses are classically antigenically distinct from viruses that circulate in humans and, therefore, are not covered by seasonal flu vaccinations. Variant viruses infect people having close contact with infected pigs, for example, workers employed in the swine industry, animal fares, etc. Droplet and surface transmission are proven methods of transmission. Although, swine influenza is not transmissible to people through properly handled and prepared pork1. Recently, the Taiwan Centre for Disease Control and Prevention (CDC) reported a type A influenza virus in October 2022 in a 7-year-old girl in central Taiwan with milder symptoms. The tests for common respiratory viruses such as respiratory syncytial virus, adenovirus, enterovirus, and rhinovirus were all negative. The pathogen was sequenced as the H1N2v influenza virus. There were six close contacts in the case, two of whom had flu-like symptoms, but the H1N2v influenza virus was not detected. The case was judged to be sporadic, with no evidence of human-to-human transmission. The virus was also not detected in any of the pigs on their family farm2. Taiwan's first human H1N2v infection was a 5-year-old girl, again, in central Taiwan, diagnosed in April 2021. The isolated virus was designated A/Taiwan/1/2021(H1N2) v. Her family also reared pigs, but after correlating the histories of the two cases regarding farms' locations, their feed suppliers, the slaughterhouses used, the routes traveled, and the genetic constitution of the two viruses, the two cases are proven to be entirely unrelated. Similar to the recent case, there was also no proof of human-to-human transmission. To date, there have been 45 cases of human infections with H1N2v across the globe, with a majority of them (91%, n=41) detected in the USA3. Phylogenetic analyses of the first case in the year 2021 revealed that the pathogen was a novel reassortant virus having hemagglutinin and neuraminidase gene segments derived from swine influenza A H1N2 viruses that may have been circulating in Taiwan for decades, and the remaining six internal genes (PB2, PB2, PA, NP, M, and NS) were from the human A (H1N1) pdm09 virus. Bidirectional transmission between humans and swine can also lead to the reassortment of genes, resulting in a novel strain4. The vast majority of human infections with variant influenza viruses do not result in a person-to-person spread. Yet, each case of human infection with a swine influenza virus should be fully investigated to rule out efficient spread so that further exposure of humans can be curbed. In the year 2012, out of 309 human infections with another variant virus H3N2v, 16 people were hospitalized, with mortality in one case. People at high risk of serious complications with variant viruses include extreme of ages, asthma, diabetes mellitus, cardiac disease, and antenatal females. The CDC continues to monitor closely for variant influenza virus infections5. In November 2015, this H1N2v virus was also detected in a nasopharyngeal sample from a 16-year-old girl from Castro City, Paraná, South Brazil. Castro is a major hub for pigs, cattle, and poultry. The patient had a fever, cough, sore throat, chest pain, and myalgia after having direct contact with pigs. To ensure early detection, surveillance should focus on geographic areas where different influenza A viruses circulate and where humans and animals are frequently in close contact . This virus was a triple reassortant, containing gene segments from subtypes H1N2, H3N2, and pandemic H1N6. The unpredictable swine-origin variant influenza viruses may possess distinct antigenicity, the ability to infect animals, and the capability for enhanced transmission, which are all other virological attributes of pandemic influenza strains. Evaluation of novel and emerging influenza viruses, aid pandemic preparedness, and conduct further research can be conducted by identifying gaps in knowledge. The information obtained using meticulous research, including the replication, capacity for spread, and transmission frequency of different virus strains, can help identify molecular markers of virulence and transmissibility. Each case of human exposure brings a risk of adaptation of these viruses to transmit in humans and possibly result in a pandemic. Features such as the ability to bind to human-like receptors and their high turnaround of replication in human cell lines, as well as in animal models, were commonly observed with H1v viruses in various studies. Conversely, in comparison to human seasonal and pandemic influenza virus strains, H1v viruses are transmitted less efficiently via air and have higher HA activation pH thresholds, indicating a relative difficulty in human adaptation. Sporadic human infection with viruses from the swine reservoir can either indicate an enhanced adaptation of these viruses to human host or these can be only dead-end spill-over events, but to elucidate that, much more evidence is needed7. There are some preventive measures warranted to curb the spread of variant viruses to humans. As per the CDC, people with high-risk factors should avoid contact with pigs; one should not eat or drink in pig areas. Ill-looking swine should be isolated immediately from the rest of the drift. Close contact with the pigs that look or act ill should be avoided at all, costs and after taking care of them, hand hygiene should be carried out with soap and running water or an alcohol-based rub, both before and after exposure to pigs and their environments. If one must work around sick people or the pigs, recommended personal protective equipment such as gloves, a face mask, or an N-95 respirator should be worn. People with high-risk factors who develop flu symptoms should give the history of any recent exposure to pigs or swine barns to their healthcare provider8,9. Ethical approval Not applicable. Sources of funding No funding received. Authors contributions R.S., A.M., R.R., and B.K.P. developed the original draft, review, and edit the manuscript. All authors read and approve for the final manuscript. Conflict of interest disclosure No conflicts of interest. Research registration unique identifying number (UIN) 1. Name of the registry: NA. 2. Unique identifying number or registration ID: NA. 3. Hyperlink to your specific registration (must be publicly accessible and will be checked): NA. Guarantor Ranjit Sah.